The metabolism of the thyroid hormones was studied in monolayer cultures of monkey hepatocarcinoma cells. The results showed the presence of a very active diodinating system for the nonphenolic ring iodines, yielding reverse triiodothyronine (rT3) from thyroxine and yielding 3,5-diiodothyronine (T2) and 3'-monoiodothyronine from triiodothyronine. There was a less active phenolic ring deiodinase yielding T2 from rT3. When the cells were starved, there was a marked enhancement of the nonphenolic ring deiodination, which probably accounts for the increased circulating levels of rT3 observed in starved animals or humans. A novel synthesis of nonphenolic ring labeled 3,5-T2 was devised as a tool for further studies on iodothyronine metabolism.